Fig. 41.17). GH stimulates IGF-I pro duction by the liver, and IGF-I then inhibits GH synthesis and secretion by the pituitary and hypothalamus in a classic “long feedback” loop. In addition, GH itself exerts negative feedback on release of GHRH through a “short feedback” loop. GH also increases somatostatin release.
GH secretion, like ACTH, shows prominent diurnal rhythms, with peak secretion occurring in the early morning just before awakening. Its secretion is stimulated during deep slow-wave sleep (stages III and IV). GH secretion is lowest during the day. This rhythm is entrained to sleep-wakefulness patterns rather than light-dark patterns, so a phase shift occurs in people who work night shifts. As is typical of anterior pituitary hormones, GH secretion is pulsatile. Levels of GH in serum vary widely (0–30 ng/ mL, with most values usually falling between 0 and 3). Because of this marked variation and the heterogeneity of circulating GH, measurement of serum GH levels is of limited clinical utility. Since IGF-I secretion is regulated by GH and possesses a longer half-life that buffers pulsatile and diurnal changes in GH secretion, it may be used to assess the status of the GH axis, especially in young patients.
GH secretion is differentially regulated depending on the physiological state. GH is classified as one of the “stress hormones” and is increased by neurogenic and physical stress. It promotes lipolysis, increases protein synthesis, and antagonizes the ability of insulin to reduce blood glucose levels. It is not surprising, therefore, that acute hypoglycemia is a stimulus for GH secretion and GH is classified as a hyperglycemic hormone. A rise in the serum concentration of some amino acids also stimulates GH secretion; administration of arginine is used for provocative testing of GH secretion. In contrast, an increase in blood glucose or free fatty acids inhibits secretion of GH. Obesity also inhibits GH secretion, in part because of insulin resistance (relative hyperglycemia) and increased circulating free fatty acids. Conversely, exercise and starvation stimulate GH secretion.
The lifetime pattern of GH secretion is shown in
Fig.
41.18 . GH secretion increases in the neonatal period as growth becomes GH and IGF-I dependent. It remains high throughout childhood and peaks during puberty, when estrogen (in females and also males via aromatization) promotes even higher rates of GH secretion. Thyroid hormone also enhances GH and IGF-I secretion to support bone growth and maturation. Adults continue to produce GH, consistent with its role in metabolism, before levels fall during senescence.